Examining the factors contributing to the association between non-albuminuric CKD and a low rate of kidney function decline in diabetes

BACKGROUND: Studies have shown that among people with diabetes, those with non-albuminuric chronic kidney disease (CKD) have a slower rate of reduction in renal function than do those with normal renal function. This suggests the presence of protective factors, the identification of which may open up targets for intervention. The aim of this study was to identify protective clinical factors and nonclinical biomarkers that contribute to the association between non-albuminuric CKD and the low rate of progression of CKD. METHODS: We tested for significant associations of several clinical factors and 33 nonclinical biomarkers with (1) normoalbuminuria and (2) a low rate of CKD progression among participants with diabetes and CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Factors significantly associated with both normoalbuminuria and a low rate of CKD progression were assessed in linear regression to estimate their potential contributions to the association between non-albuminuric CKD and rate of CKD progression. RESULTS: Systolic blood pressure (SBP), glycated A1c (HbA1c), estimated glomerular filtration rate (eGFR) and six biomarkers [β-trace protein (BTP), kidney injury molecule (KIM-1), fibrinogen, fractalkine, brain natriuretic peptide (BNP) and high-sensitivity troponin-T (hsTnT)] were associated with both normoalbuminuria and a low rate of eGFR decline. The univariate β-coefficient for normoalbuminuria was 0.93 [95% confidence interval (CI): 0.82, 1.05]. When all associated factors and biomarkers were included, the regression coefficient decreased to 0.54 (95% CI: 0.40, 0.67). The factors that contributed to the association between non-albuminuric CKD and low rate of eGFR were lower levels of SBP, HbA1c, BTP, KIM-1, hsTnT, BNP, fibrinogen and fractalkine. CONCLUSION: Lower levels of SBP and biomarkers that have pro-inflammatory and vascular modulating features may explain up to 40% of the association between non-albuminuric CKD and low rate of CKD progression. Further investigation of these biomarkers may lead to therapeutic interventions.